The biological revolution has led to the ability to determine natural proteins, to modify such natural proteins to change their properties, and to synthesize new proteins to obtain unique properties. The size of the proteins of interest may vary from small oligopeptides of about 14 amino acids or more, such as somatotropin, angiotensin, bradykinin, etc. to proteins of 300 kD (kiloDaltons) or greater. Chemical synthesis has been developed to the point of automation, where small oligopeptides can be efficiently synthesised. However, as the polypeptide chain is extended, the yield of the end product decreases exponentially with increasing length of the polypeptide chain. This is due to racemization of the amino acid .alpha.-carbon, incomplete elongation of individual polypeptide chains, inaccurate bonding and removal of protective groups, and the like. These factors impose serious difficulties on the purification of the end product and drastically increase the cost of the polypeptide product. Impurities having a different amino acid sequence from the desired sequence can have detrimental effects in the case of therapeutic polypeptides.
Expression of polypeptides or proteins in microorganisms by means of genetic engineering also has numerous limitations. These are associated with difficult isolation of the expression product from the transformed cells, lethality of the DNA sequence or product on the host cell, proteolytic degradation of the expression product, and difficulties in isolation and purification of the product from the host proteins. Small polypeptides are readily degraded by the intra- and intercellular proteases due to the absence of a compact spatial structure of the polypeptides.
There is, therefore, substantial interest in finding alternative techniques which allow for the efficient production of polypeptides while lacking one or more of the difficulties associated with present day techniques.